Dissertation
Dissertation > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Myocardial diseases > Myocardial infarction

Screening of Serum Metabolic Markers on Acute Myocardial Infarction Patients

Author ZhangFengMei
Tutor LiuShuYe
School Tianjin Medical University
Course Clinical Laboratory Science
Keywords metabolomics acute myocardium infarction liquid chromatographyMass spectrum
CLC R542.22
Type Master's thesis
Year 2013
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Objectives With the development of metabolomics, more and more focuses have been put on how to imply this method in medical studies and practices. In this study, through analyzing the acute myocardium infarction patients serum metabolite profiles tested by the ultra performance liquid chromatography combined with a LTQ Orbitrap XL mass spectrometry (UPLC-LTQ Orbitrap XL MS), is to establish a disease distinguishing model and to select characteristic metabolites with potential clinical diagnostic value. Serum metabolic profiling of acute myocardium infarction patients was performed to explore how to use the metabolomics method in investigating the mechanism of diseases development through comparing different clinical disease states and discovering feature metabolites for monitoring and assessing cirrhosis development and constructing discriminate models based on the selected feature metabolites using pattern recognition methods.Methods UPLC-LTQ Orbitrap XL MS platform was used to analyze42AMI (acute myocardium infarction) patients (34for model group and8for validation group) and35health volunteers (28for model group and7for validation group). The Data was pretreated and normalized by Mzmine2.0. Through PCA (principal component analysis) and OPLS-DA (orthogonal partial least squares discriminant analysis) of SIMCA-P+12.0.1.0, a disease distinguishing model was established. After that, the VIP (variable importance in projection) values, variable confidence intervals in the VIP plot and coefficient plot and non parameter test were used to select feature ions which can separate acute myocardium infarction patients and26health volunteers in the two-class OPLS-DA models, and these ions were then identified and assigned to corresponding metabolite. Then SPSS17.0was used for statistical analysis.Results PCA (R2X=75.6%, Q2=39.7%) model and OPLS-DA (R2Y=97.8%, Q2=97.0%) model were established on42acute myocardium infarction patients versus35health volunteers,36characteristic ions were selected and19ions were identified. These identified ions were mainly involved in Phospholipid metabolic pathway. Glycerophospholipids decreased in AMI group. At the same time, sphingophospholipids, excepted for Phytosphingosine, increased in AMI group, including Sphinganine, Sphingosine and Glucosylceramide. At the same time, the study also found that substances associated with acute myocardial infarction, such as Linoleyl carnitine, Oleoylcarnitine,2-Phenylaminoadenosine.Conclusions Characteristic ions that selected by using metabolic profiling technology had significant distinguishing ability for acute myocardium infarction patients and health control. These ions were considered to be potential diagnostic biomarkers and benefit in further clinical study as novel drug targets. And, after analysis of the identified metabolites, we found that tested2-Phenylaminoadenosine, long-chain acyl carnitine and phospholipids in serum with UPLC-LTQ Orbitrap XL MS become more effective means of monitoring and evaluation of myocardial infarction.

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